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Current Molecular Pharmacology

Morteza Karimian, Hamidreza Famitafreshi, Sulail Fatima
INTRODUCTION: Addiction to drugs of abuse is a devastating condition which results in deterioration of brain functioning. On the other hand, social isolation also produces cognitive deficits such as learning and memory impairment. This study was designed to evaluate the potential negative synergistic effects of social isolation and morphine addiction on brain functions. METHODS AND MATERIAL: One hundred and two Sprague-Dawley rats were randomly divided into four groups for assessing neurogenesis and behaviour: group-housed, isolated, morphine-treated group-housed and morphine-treated isolated groups...
August 22, 2016: Current Molecular Pharmacology
Marcos Brandão Contó, Marco Antonio Campana Venditti
Epilepsy is one of the most prevalent neurological disorders worldwide, but its underlying mechanisms have not yet been clarified. Among the possible molecular mechanisms that underlie its occurrence are those that are responsible for the neuronal ionic gradient, including the transmembrane enzyme Na+,K+-adenosine triphosphatase (ATPase). Na+,K+-ATPase plays an important role in controlling neuronal excitability, and it is believed to be related to the pathophysiology of epilepsy. However, the specific isozymes that may be related to this neurological disorder remain to be determined...
April 7, 2016: Current Molecular Pharmacology
Behzad Yeganeh, Amir A Zeki, Nicholas J Kenyon, Saeid Ghavami
No abstract text is available yet for this article.
January 14, 2016: Current Molecular Pharmacology
José César Rosa, Marcelo de Cerqueira César
Several neurological diseases such as bipolar disorders and schizophrenia are linked to impaired brain energy metabolism. A key feature of brain bioenergetics is hexokinase (HK) binding to the outer mitochondrial membrane through the voltage dependent anion channel (VDAC). This has metabolic consequences, with phosphorylation of glucose by mitochondrially bound hexokinase being closely coupled to production of substrate ATP by intramitochondrial oxidative phosphorylation. Additionally, binding of HK to mitochondria inhibits Bax-induced cytochrome c release and apoptosis...
January 12, 2016: Current Molecular Pharmacology
S Zahra Bathaie, Mahboobeh Ashrafi, Mahshid Azizian, Fuyuhiko Tamanoi
Mevalonate (MVA) is synthesized from 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) by HMG-CoA reductase (HMG-CoAR). MVA is further metabolized to farnesyl pyrophosphate (FPP), a precursor of cholesterol and sterols. FPP is also converted to geranylgeranyl pyrophosphate, and these lipids are used for post-translational modification of proteins that are involved in various aspects of tumor development and progression. Many studies showed that the MVA pathway is up-regulated in several cancers such as leukemia, lymphoma, multiple myeloma; as well as breast, hepatic, pancreatic, esophageal and prostate cancers...
January 12, 2016: Current Molecular Pharmacology
Eftekhar Eftekharpour, Nagakannan Pandian, Mohamed Ariff Iqbal, Qi Min Chen
The mevalonate pathway has been extensively studied for its involvement in cholesterol synthesis. Inhibition of this pathway using statins (3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors; HMGR inhibitors) is the primarily selected method due to its cholesterol-lowering effect, making statins the most commonly used (86-94%) cholesterol-lowering drugs in adults 1. This pathway has several other by-products that are affected by statins including GTPase molecules (guanine triphosphate-binding kinases), such as Rho/Rho-associated coiled kinase (ROCK) kinases, that are implicated in other diseases, including those of the central nervous system (CNS)...
January 12, 2016: Current Molecular Pharmacology
Leonardo Ermini, Martin Post, Isabella Caniggia
The mevalonate pathway synthesizes intermediates and products such as cholesterol and non-sterol isoprenoids that are crucial for cell survival and function. In the human placenta, the prenylation of proteins, rather than cholesterol synthesis, represents the main "metabolic target" of mevalonate metabolism. Major cellular functions depend on isoprenylation including proliferation, migration, metabolism and protein glycosylation that are all crucial for proper development of the embryo and the placenta. Statins are inhibitors of HMG-CoA reductase, the enzyme that catalyzes the reduction of HMG-CoA to mevalonic acid by NADPH...
January 12, 2016: Current Molecular Pharmacology
Kristin A Gabor, Michael B Fessler
It has become increasingly recognized that cholesterol and lipoproteins play significant roles in both lung physiology and the innate immune response. It is now known that the innate immune response and the cholesterol biosynthesis/trafficking network regulate one another, with important implications for pathogen invasion and host defense. The activation of pathogen recognition receptors and downstream cellular host defense functions are critically sensitive to cellular cholesterol. Conversely, microorganisms can co-opt the sterol/lipoprotein network in order to facilitate their own replication...
January 12, 2016: Current Molecular Pharmacology
Mohammad Hashemi, Reyhane Hoshyar, Sudharsana R Ande, Qi Min Chen, Claudia Solomon, Anne Zuse, Mohammad Naderi
The cholesterol biosynthesis pathway, also referred to as the mevalonate (MVA) pathway, is responsible for the biosynthesis of two key isoprenoids: farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). Post-translational modification of small GTPases by FPP and GGPP has captured much attention due to their potential contribution to cancer, cardiovascular and neurodegenerative diseases. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) catalyzes the conversion of HMG-CoA to MVA, and is the rate-limiting step in the biosynthesis of cholesterol...
January 12, 2016: Current Molecular Pharmacology
Xiaodan Jiao, Niloufar Ashtari, Maryam Rahimi Balaei, Qi Min Chen, Ilnaz Badbezanchi, Shahla Shojaei, Adel Marzban, Nima Mirzaei, Seunghyuk Chung, Teng Guan, Jiasi Li, Jerry Vriend, Shahram Ejtemaei Mehr, Jiming Kong, Hassan Marzban
The mevalonate cascade is a key metabolic pathway that regulates a variety of cellular functions and is thereby implicated in the pathophysiology of most brain diseases, including neurodevelopmental and neurodegenerative disorders. Emerging lines of evidence suggest that statins and Rho GTPase inhibitors are efficacious and have advantageous properties in treatment of different pathologic conditions that are relevant to the central nervous system. Beyond the original role of statins in lowering cholesterol synthesis, they have anti-inflammatory, antioxidant and modulatory effects on signaling pathways...
January 12, 2016: Current Molecular Pharmacology
Pooneh Mokarram, Javad Alizadeh, Vahid Razban, Mahdi Barazeh, Claudia Solomon, Soudabeh Kavousipour
The metabolic steroid hormones, 17β stradiol (E2) and testosterone play roles in several functions including carbohydrate, lipid and protein metabolism, cellular signaling, cell proliferation, and cancer promotion. Steroid hormones have long been characterized as cell proliferation and differentiation regulators and are closely related to the development of breast and prostate cancers. In addition, cholesterol metabolism, mainly in adipose tissue, leads to the production of steroids and cytokines, thus increasing the risk of metabolic syndrome, obesity, and ER+ breast cancer in postmenopausal women...
January 12, 2016: Current Molecular Pharmacology
Alison L Müller, Darren H Freed
Inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase by pharmaceuticals, commonly referred to as statins, has proven to be an effective and efficient way to reducing cholesterol levels in patients. As a result of this intervention, mevalonate production, formed during cholesterol synthesis, is inhibited. Mevalonate is the precursor to a variety of crucial downstream products, including those involved with the mitochondrial electron transport chain, and localized activation of small GTPases. Statins have also been observed to induce changes of the immune system, favouring a reduced pro-inflammatory phenotype...
January 12, 2016: Current Molecular Pharmacology
Neil C Thomson
Immunomodulatory effects of statins in vitro and in experimental models of asthma and COPD could potentially be relevant to the treatment of chronic airway diseases. This article provides an overview of the evidence from the key clinical studies on the effects of statins on clinical outcomes and inflammatory biomarkers in asthma and COPD. Future directions for clinical studies of statins in asthma and COPD are discussed. A small number of randomized controlled trials (RCTs) in adults with mild to moderate asthma suggest that short-term statin treatment does not improve lung function or symptom control, except for a possible improvement in quality of life and symptoms in smokers with asthma...
January 12, 2016: Current Molecular Pharmacology
Robert P Young, Raewyn J Hopkins
Current evidence suggests that persisting and/or exaggerated inflammation in the lungs initiated by smoking, and up-regulated through genetic susceptibility, may result in lung remodelling and impaired repair. The mevalonate pathway, through its modifying effects on innate immune responsiveness, may be involved in these processes providing a plausible pathogenic link between the development of chronic obstructive pulmonary disease (COPD) and lung cancer. The mevalonate pathway, mediates these effects through important intra-cellular signalling molecules called guanine phosphate transferases (GTPases) such as Rho-A...
January 12, 2016: Current Molecular Pharmacology
Mario D Galigniana
No abstract text is available yet for this article.
2016: Current Molecular Pharmacology
Mariana Lagadari, Sonia A De Leo, Maria F Camisay, Mario D Galigniana, Alejandra G Erlejman
The fine regulation of signalling cascades is a key event required to maintain the appropriate functional properties of a cell when a given stimulus triggers specific biological responses. In this sense, cumulative experimental evidence during the last years has shown that high molecular weight immunophilins possess a fundamental importance in the regulation of many of these processes. It was first discovered that TPR-domain immunophilins such as FKBP51 and FKBP52 play a cardinal role, usually in an antagonistic fashion, in the regulation of several members of the steroid receptor family via its interaction with the heat-shock protein of 90-kDa, Hsp90...
2016: Current Molecular Pharmacology
Ji Wu
No abstract text is available yet for this article.
September 28, 2015: Current Molecular Pharmacology
Xiaowei Jin, Tongxiang Lin, Yang Xu
With their capability to undergo unlimited self-renew and to differentiate into various functional cells, human pluripotent stem cells, including embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), hold great promise in regenerative medicine to treat currently incurable diseases. Significant progress has been achieved in differentiating pluripotent stem cells into various functional cells, such as pancreatic  cells, neural cells, hepatocytes, and cardiomyocytes. In addition, three hESC-based therapies to treat spinal cord injury, macular degeneration and type I diabetes have entered clinical trial...
September 28, 2015: Current Molecular Pharmacology
Shihua Wang, Pengchao Xu, Xiaoxia Li, Xiaodong Su, Yunfei Chen, Li Wan, Linyuan Fan, Kan Yin, Yan Liu, Robert Chunhua Zhao
Mesenchymal stem cells (MSCs) represent a new therapeutic paradigm for a number of diseases because they possess unique biological characteristics such as multipotency, immunomodulation and production of cytokines. Currently, 425 MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy of MSCs. Here, we provide an overview of the clinical status of MSCs by searching the public clinical trials database http://clinicaltrials...
September 28, 2015: Current Molecular Pharmacology
Xuqing Liu, Tao Sun
Microcephaly is a clinical condition defined as a reduction in head circumference and brain volume. The abnormal brain size may result from pathological neural stem cell (NSC) proliferation, survival, differentiation and migration during the development of the cerebral cortex. This process is controlled by many factors, including microRNAs that normally silence target genes at the posttranscriptional level. In this review, we will discuss the roles of microRNAs involved in different stages of the cortical development to shed light on the pathogenesis of microcephaly...
September 28, 2015: Current Molecular Pharmacology
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